Radiograph density detection device

ABSTRACT

A system for radiographic tissue density evaluation includes a cassette for exposure to an X-ray source, where the cassette is configured to obtain information to perform intensity standardization of a captured radiographic image of a subject, a calibration bar with a predetermined radiographic signature on or within the cassette to serve as reference for performing the intensity standardization, and a software program to perform analysis on and to provide a display of the captured radiographic image. The cassette also includes a radio-opaque backing with a spatial homogenous X-ray radiographic signature used to estimate a source-detector geometrical inhomogeneity.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/524,044, filed May 3, 2017, now U.S. Pat. No. 10,667,777, which is aNational Stage Application of International Application No.PCT/US2015/059530, filed Nov. 6, 2015. This application claims priorityfrom U.S. application Ser. No. 15/524,044, International Application No.PCT/US2015/059530, and U.S. Provisional Patent Application Ser. No.62/076,340, filed Nov. 6, 2014. Each of these applications is herebyincorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention in general relates to the field of imaging and inparticular to an improved system and method for providing X-rayradiographs with quantitative and standardized levels for bone and othertissue density evaluations.

BACKGROUND OF THE INVENTION

Bone density is an important measure of bone health, and in some cases,systemic health of a subject. Low bone density has been identified as arisk factor for fractures (especially long, spinal vertebrae and pelvicbones), degenerative joint disease (arthritis), pain, decreased activitylevels, certain disease states (bone cancers, select endocrine diseases,obesity, etc.), medications that result in bone loss, dental disease(due in part to loosened teeth) and even as a measure of welfare. Bonedensity disorders are recognized in both humans and non-human animals.By identifying poor bone density, clinicians have the opportunity torecognize and diagnose certain diseases earlier (as opposed to waitingfor more overt disease to develop) and develop risk assessment protocolsand hopefully preventative measures.

In addition, other tissue densities may also show promise for diseaseidentification and serve as prognostic markers of certain diseases. Thisincludes identifying the density of foreign materials that may have animpact on health. For example, by quantifying the density of ingestedmetals clinicians may be able to determine if conservative therapyresults in successful dissolution of the item (by measuring decreasingdensity over a set period of time). Additionally, non-bone tissues thatare more or less radiodense than “normal” may indicate a disease processis present. As an example, hyperadrenocorticism, certain kidneydisorders and select toxins can increase mineralization in soft tissues.

Furthermore, low bone density also correlates with poor diet, lack ofexercise, and lack of natural light exposure (especially for diurnalspecies), and may be compared to “normal” to better determine welfare ofanimals kept in captivity. The ultimate goal would be to improveconditions for captive animals by improving nutrition, activity leveland natural UV light exposure, especially for those animals that haverestricted access to natural light, sufficient room to ambulate, and/orare on a poor diet. Bone density has been studied in laboratory animalsand in poultry species, where low bone density has been found to be acommon problem in captive production birds. Advanced cases may easily berecognized by strikingly poor bone density and sometimes folding typefractures on standard radiographs, as shown in the example in FIG. 1.However, studies in other animals are critically lacking primarily dueto the cost of diagnostic equipment. As a result, large scale studiesthat correlate bone/tissue density with health and disease states arenot possible without substantial funding.

Advances in medical imaging technology have allowed noninvasivevisualization and measurements of a wide variety of anatomy andfunctions of the body. Radiodensity or radiopacity refers to therelative inability of electromagnetic radiation, particularly X-rays, topass through a particular material. Radiolucency indicates greatertransparency or “transradiancy” to X-ray photons. Materials that inhibitthe passage of electromagnetic radiation are called radiodense, whilethose that allow radiation to pass more freely are referred to asradiolucent. The term refers to the relatively opaque white appearanceof dense materials or substances on radiographic imaging studies,compared with the relatively darker appearance of less dense materials.Because calcified tissues such as bone are radio-opaque, X-ray basedimaging including projection radiography (or X-ray radiography) andcomputed tomography (CT) are the most commonly used modalities forassessing bone morphology.

Although X-ray radiography offers the highest spatial resolution usefulfor detecting, for example, hairline fracture in a bone, due to the lackof calibration and the physics of image formation, X-ray radiographyintensities are generally only qualitative in nature. Due to itsqualitative nature, X-ray radiographs give clinicians only subjective,relative evaluation of tissue density. As a result, standardradiographs, which are common in private practice, cannot be used toprovide scientifically meaningful data on bone/tissue density. Incontrast, CT intensities are both quantitative and standardized acrossall scanners, and are the best (in terms of speed and resolution) forvisualizing the skeletal system and some soft tissue structures.

There are several reasons why existing X-ray radiography is not suitedfor quantitative intensity-based evaluations. Most X-ray radiography andCT instruments employ a “point source” for generating the X-ray. As thegenerated X-ray radiates away from the source, the intensity of theX-ray decreases as the inverse-square of the distance. Moreover, as theX-ray arrives at the detector, which is normally flat, unless theincident angle is perpendicular to the detector, the intensity of theX-ray is further diminished as the X-ray beam is spread across a biggerarea. Combined, even when the point source is aimed directly andsquarely at the detector, the “source-detector geometry” imposes aninherent variability on X-ray intensity across the detector. Whether aconventional film or digital detector is used, spontaneous processes inthe detector (e.g., intrinsic electronic charges in the digitaldetector) contributes to baseline intensity in the X-ray image even whenthe source is completely turned off. Due to the properties ofexposure-to-intensity conversion, the conversion might not be linear(i.e., doubling the exposure may not result in doubled brightness on theimage). In addition to the baseline and nonlinear responses, alldetectors have finite response “dynamic range.” Unless the exposure isoptimized to the range, under-exposure can lead to patches of uniformlydense regions (regardless of variability of the underlying anatomy),whereas over-exposure can lead to apparent disappearance of low-densityregions.

In computed tomography (CT), all of the above issues with X-rayradiography are effectively addressed by the so-called “dark-lightcalibration” and “exposure optimization” procedures that are performedas part of the CT acquisition. The dark-light calibration essentiallyinvolves obtaining scans with and without the source turned on, andsubtracts the obtained values from all subsequent acquisitions. Exposureoptimization involves an iterative process of scans and intensityanalysis to find the exposure setting that is just below the upperdetector dynamic range. Separately, all CT-obtained intensities arestandardized by normalizing the intensities to those for air and water,such that air and water will have exactly 1000 and 0 “Hounsfield Units,”respectively, in all scanners.

Even though CT provides the best speed and resolution for visualizingthe skeletal system, the cost of CT scans is prohibitive and the limitedavailability of CT equipment makes its wide usage impractical in mostveterinary and human point-of-care practices. Thus, there exists a needfor improved systems and methods that provide skeletal visualizationsthat are comparable to CT scans but at a lower cost and with lowerdosimetry.

SUMMARY OF THE INVENTION

A method for radiographic tissue density evaluation is provided thatincludes capturing a radiographic image of a material with an X-rayimage collection cassette. The cassette includes components (eitherbuilt in or attached to the cassette) that allow for performingintensity standardization of the captured radiographic image. A spatialhomogenous backing alone, at least one calibration bar, or a combinationthereof serve as a reference for such standardization through backgroundsubtraction and known absorption, respectively. The radiographic imageis analyzed to determine spatially resolved tissue/subject density inthe biological or non-biologic material. The biological material can bea biopsy, a microorganism, an organ, organelle, or a living subject suchas a human or an animal, or a cadaver. The non-biologic subject can beany device, structure or other item not composed of biologic material. Asystem for performing the method is also provided that includes astandard or specialized X-ray image recordation cassette and softwarefor radiographic image analysis.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention is further detailed with respect to the followingdrawings. These figures are not intended to limit the scope of thepresent invention but rather illustrate certain attributes thereof.

FIG. 1 is a prior art radiograph of a juvenile barn owl (Tyto alba) withsevere metabolic bone disease and multiple folding fractures (arrows);

FIGS. 2A-2C are an as taken a radiograph of an ex vivo hamster (FIG. 2A)with an intensity calibration bar (top of image) according to anembodiment of the invention, background isolation (FIG. 2B) and theimage of FIG. 2A after subtraction of the background of FIG. 2B (FIG.2C);

FIGS. 3A-3D are color density maps of two cockatiels according to thepresent invention, with FIGS. 3A-3B representing images for the firstcockatiel, and FIGS. 3C-3D representing images for the second cockatiel;and

FIGS. 4A-4B are schematics of a cassette showing a backing andcalibration bar in two different inventive embodiments.

DESCRIPTION OF THE INVENTION

The present invention has utility as a method and system to make X-rayradiographs sufficiently quantitative and standardized for bone, othertissue and non-biologic subject density evaluations. Embodiments of theinventive X-ray radiograph methodology and system provide a costeffective diagnostic tool that may be used in daily practice withexisting X-ray radiography equipment already present in many clinics andhospitals to ultimately produce large volumes of scientifically validdata and useful diagnostic and prognostic information.

Embodiments of the inventive radiograph based bone, tissue, non-biologicsubject density determination system are designed to visually andnumerically identify bone and other densities using digital radiographs.The values generated are based on a universal scale, different fromHounsfield units, that can be standardized from radiograph to radiographand across machines assuming proper radiograph positioning and technique(for the subject in question) is used and radiographic equipment isfunctioning properly. The inventive system may be used as a low costalternative to more expensive density imaging methods such ascomputerized tomography (CT) and Dual-energy X-ray absorptiometry (orDEXA) scans.

Embodiments of the invention may be used in any situation whereradiographs are taken—standard limb or whole body images, dental,clinical patient, research—and on potentially any animal includinghumans. Embodiments of the inventive X-ray radiograph methodology andsystem may also potentially be used on plants, minerals, metals, manmadematerials and any other naturally occurring or foreign substance,industrial equipment, and other objects and structures, serving as aninexpensive way of collecting density information, with radiation dosingthat is less than that of CT scanning. Materials suitable for densityinterrogation according to the present invention illustratively includea whole multicellular organism, a microbe, a virus, or parts of anorganism (as in a specific organ, organelle, or tissue), ornon-biological materials such as castings. The applications includeobvious health data, but could be used as a screening tool for densityvariations in just about any material or object. A living human oranimal or cadaver of the same are exemplary materials in a clinicalsetting.

To form the inventive Radiograph Density Detection Device (RDDD)(hereinafter referred to as a radiographic device, or simply the device)a component may be added to a conventional X-ray film cassette(internally as a part of the cassette or peripherally attached to thecassette) and subsequently incorporated into radiographs forinterpretation. The incorporated device acts as a standard against whichanimal, human, non-biological, and other tissue densities can bemeasured. An inventive software based program is provided to interprettissue densities (including bone) to ultimately identify low, normal, orhigh values compared to “normal” densities. Densities created by thesoftware may be presented in a variety of forms illustratively includingdensity associated colors and absolute numerical values and can givelocal regional and whole subject values. In some inventive embodiments,orthogonal views of the same material can be used to by the software tomathematically generate volumetric color and numerical values for thematerial. The inventive device provides the diagnostician real data asto the density of normal and foreign body tissues to aid in diseasediagnosis and prediction of health of a subject either human or animal.Non-biologic material densities can also be rapidly studied as withbiologic materials to, for example, identify internal porosity or voidsin a casting.

Embodiments of the inventive device and method provide a low cost andrelatively accurate (within an acceptable tolerance or error)alternative to CT or other more expensive and generally unavailablediagnostic tests that evaluate bone and other tissue densities inpatients, with generally lower radiation exposure. Embodiments of thedevice may be used on digital radiograph machines which are nowcommonplace in human and animal medical facilities with embodiments ofthe inventive software to convert the images obtained into tissuedensity scores. Embodiments of the invention require minimalmodification or additional procedure to the effort involved in taking aconventional X-ray radiography. It is appreciated that an X-raymicroscope is also used to obtain density information regardingmaterials smaller than a few millimeters.

The following are non-limiting illustrative examples of specific typesof disorders where evaluation using the above RDDD system may improvediagnosis and potentially treatment:

Soft tissues: muscle contraction; myositis ossificans; vascular diseases(mineralization, atherosclerosis); tenosynovitis; tendon avulsion;inflammation (traumatic, parasitic, fungal, bacterial, neoplastic,autoimmune, toxins, thermal burns, freezing injury, idiopathic,nosocomial, exogenous drug induced, endogenous drug induced, etc.);general abnormal mineralization or mineral deposits; tissue disruption;duplicate, hypertrophied, atrophied, missing, reversed or misplacedorgans/tissues; foreign bodies, granulomas, calculi formation,calcinosis cutis; panniculitis; intervertebral disk disease; periodontaldisease; joint/tendon/ligament ruptures; retained cartilage cores;fibrotic myopathy; and general and organ specific neoplasia. Diagnosisof any disorder that alters the density of soft tissues may potentiallybenefit from the RDDD.

Bone tissues: osteomalacia; osteoporosis; osteodystrophy; osteomyelitis(traumatic, parasitic, fungal, bacterial, neoplastic, autoimmune,toxins, thermal burns, freezing injury, idiopathic, nosocomial,exogenous drug induced, endogenous drug induced, etc.); panosteitis;vitamin A toxicity; periosteal inflammation (traumatic, parasitic,fungal, bacterial, neoplastic, autoimmune, toxins, thermal burns,freezing injury, idiopathic, nosocomial, exogenous drug induced,endogenous drug induced, etc.); osteoarthritis/degenerative jointdisease; rheumatoid arthritis; erosive arthritis (single or poly);non-erosive arthritis (single or poly) (traumatic, parasitic, fungal,bacterial, neoplastic, autoimmune, toxins, thermal burns, freezinginjury, idiopathic, nosocomial, exogenous drug induced, endogenous druginduced, etc.) osteitis (traumatic, parasitic, fungal, bacterial,neoplastic, autoimmune, toxins, thermal burns, freezing injury,idiopathic, nosocomial, exogenous drug induced, endogenous drug induced,etc.); periosteal bruising; fractures; multiple cartilaginous exostoses;diskospondylitis; Legg-Calvé-Perthes disease; osteochondrosis; septicarthritis (traumatic, parasitic, fungal, bacterial, neoplastic,autoimmune, toxins, thermal burns, freezing injury, idiopathic,nosocomial, exogenous drug induced, endogenous drug induced, etc.);craniomandibular osteopathy; bone cysts; hypertrophic osteopathy;nutritional secondary hyperparathyroidism; renal secondaryhyperparathyroidism; mucopolysaccharidosis; bone mutilation from injury,infection, self-trauma, other; monitor bone biopsy and graft/implantsites, and more. Diagnosis of any disorder that alters the density ofbone may potentially benefit from the RDDD.

With respect to FIGS. 4A and 4B, in which like numerals have likemeaning when ascribed to different drawings, a specific embodiment ofthe inventive device 40 or 50 in the form of a flat-bed cassette 42 isconfigured for placement under a human subject or other material as partof the regular X-ray radiography exam, in order to make X-rayradiography more quantitative and standardized. The cassette 42 capturesinformation to perform intensity normalization and standardization, atlocations (e.g., field hospitals) where care is rendered. The cassettemay have (a) a minimally radio-opaque backing 44 which may be made ofacrylic polymer or other radiolucent material or an image receptivelayer that directly converts X-ray information into a digital signal, ofuniform thickness whose X-ray radiographic signature can be used toestimate the source-detector geometrical inhomogeneity, and (b) acalibration bar 46 consisting of known materials and known thicknesswhose radiographic signatures can serve as references forstandardization. In inventive embodiments the calibration bar acting asthe reference device may fit on top of or within a radiograph cassettethat is composed of a set of standard density items. In order toaccommodate the wide range of X-ray exposures that may be encountered inthe field, separate sets of the inventive cassette may be configured foruse with low, medium and high exposures in part based on the size thesubject.

The standard X-ray cassette 42 is utilized. The cassette 42 may besquare, rectangular or specially shaped and sized for the subject. Acalibration bar 46, composed of multiple materials of known density andproper size to account for changes in the X-ray direct and incidentangles and cassette and subject sizes, may be built into the cassette42, simply placed on top of the cassette 42 or interchangeably insertedinto the cassette 42. Specially designed cassettes would house theinterchangeable port or permanent location of the calibration bar. It isappreciated that a novel cassette is developed in which the entirecassette serves as the calibration bar such that additional componentsare not required.

The terms “low,” “medium,” and “high” are in the context of X-rayexposure for a given X-ray source. It is appreciated that the thicknessand radio-density of the material being investigated are importantaspects in deciding the exposure. Additionally, X-ray cassettes may havebuilt-in calibration bars or similar devices that cover a larger rangethan afforded by individual and interchangeable bars.

The calibration bar on embodiments of the cassette is configured to havea sufficiently wide range and graduated radio-opacity (set of standarddensity items) for the entire dynamic range of exposure encountered inpractice. This reference range provides densities which are compared tothe subject's different tissues. In embodiments, software is configuredto quickly interpret the information and provide real time data as tothe densities of set and user defined points (a portion of a bone forexample) as well as set and user defined regions (a whole bone forexample).

Embodiments of the inventive software are configured to performnumerical operations to convert raw X-ray radiographic intensity intostandardized metrics to be used in, for example, evaluating bonedensity. The software may be installed on a server or computer that islocated in the same hospital or location where the scans are performed,or the software may be on a remote server or offered as a softwareon-demand service in the cloud that is accessed over the Internet. Theimages may be transmitted to a central location to be processed andanalyzed by the same persons, although the software for the analysis canalso be distributed to the field locations. The inventive softwareincludes capabilities to (a) estimate the background (created by theinstrument source-detector geometry and baseline responses) and subtractit from the raw image, and (b) convert the grayscale images intocolor-coded images (an intuitive colormap) based on the referencematerials, since the human eye can more readily discern different colorsover different shades of grey. In a specific embodiment, the colormapscale follows the visible spectrum with normalized radiodensity valuesfrom 0-100 corresponding to a color progression from red to violet, orvice versa.

Because of the inherent variation in background intensity generated inX-ray radiography (in part due to the physics of x-rays diverging fromthe perfect perpendicular orientation of the central ray and thereceptor plate), another embodiment of the inventive software is toadjust for this variation and create a homogeneous background on theimage. FIGS. 2A-C demonstrate the gradient naturally present in X-rayimages. Without correction, this gradient affects the visual brightnessof images and ultimately results in variation, of what may be the exactsame density, from one side of the film to the other. The inventivesoftware corrects for this gradient across the X-ray image creatingdensity values consistent with the true density of the subject. Inanother embodiment of the inventive software enhancement tools added tothe image, by the native digital image processing software, areaccounted for and counteracted, minimized or otherwise adjusted for toreduce their effect on further density processing. Such digital imagingtools, such as sharpening type tools, are common with digital imagingsoftware. These tools are designed to help the viewer discern subtletiesin the greyscale of the image. Sharpening and shadowing can help definelines in between various grey scales and are often used to help theimage visually “pop.” However, these shadows, sharpenings and otherchanges can artificially affect the density of certain subjectattributes and must be considered. The inventive software also works toaddress some or all of these enhancement tools that may bepresent—especially those that may affect density readings. Correctionmay include working with the manufacturer of the native software to turnoff these features or by adjusting for the changes created from theenhancement tool(s).

The ability of the inventive software to convert the grayscale imagesinto color-coded images allows for creation of density color maps thatmay be adjusted through a series of density ranges. This allows theimage to be intensified (amplify the density signal) for specificregions as needed. The adjustable intensity range may be applied to anyimage and directly compared between images of different subjects.Embodiments of the inventive software generate real values thatcorrespond to the density range (whether amplified or not), whichassigns a “number” on the density value that can also be compared withthe subject and between subjects.

Specific embodiments of software algorithms used for image correctioncreate a correction methodology that will produce quantitative values ofradio-opacity in X-ray radiography that are within 5-15% accuracy of thevalues measured by CT. In a preferred embodiment radiographic densityinformation is within 95%, or greater, correlation of CT density values(Hounsfield units). The radiographic density score is consistent betweenany X-ray machine using the inventive flat-bed cassette and onlyrequires proper patient/subject positioning and the use of the inventiveoperating software. The user would simply click a “button” and get acolor coded density map for an overview of density, regional, and evenlocalized views. Real “density” values may be collected regionally,locally, and even in very specific spots/pixels on a subject. Thesedensity values may be used to identify variations from “normal” orexpected values.

In inventive embodiments identified combinations of materials andthicknesses that have discrete, gradated radio-opacity suitable for theconstruction of a radio-opacity calibration bar are formed. Theidentification of material includes the backing board and/or itsthickness in order to accommodate the X-ray exposures that will be usedfor different-sized animals and subjects.

EXAMPLES Example 1

FIGS. 2A-2C show a radiograph of an ex vivo hamster (FIG. 2A) with anembodiment of the intensity calibration bar (top of image). In theradiograph of FIG. 2A, there is a conspicuous background that increasesin intensity (dark to light) from left to right of the image. Thenon-uniform background is isolated (FIG. 2B), which contributes toapproximately 10-15% of the intensity variation across the image in thisspecific example. After subtracting the background, the corrected image(FIG. 2C) shows visibly improved contrast and detail, especially in theanimal head. Importantly, the intensities can now be assigned bonedensity values with more certainty by cross-referencing with thecalibration bar.

Example 2

Validation of embodiments of hardware-software methodology in makingX-ray radiography quantitative is obtained with radiographs of differentobjects as well as ex vivo animals of varying sizes, and performingpost-analysis corrections, and compare the corrected radiographsdirectly with CTs of the identical objects and animals. The results maybe used as feedback for improving the software algorithms of thecorrection.

Example 3

FIGS. 3A-3D are corrected radiographs (X-ray image) with color densitymaps of two cockatiels. FIGS. 3A and 3B refer to cockatiel 1, and FIGS.3C and 3D refer to cockatiel 2. The animals are approximately the samesize and radiographs were completed on the same machine with identicalsettings. FIGS. 3A through 3D show the calibration bar (represented bycircles of varying colors and, subsequently, densities). The birds werefirst radiographed with a standardized calibration bar creatingunprocessed images. Next the same images underwent post-processing toeven the background gradient. The second step ensures that all, or atleast most, points on the image have been adjusted for the gradientvariation and is crucial to the next step of assigning density values tothe tissues. FIGS. 3A and 3C show cockatiel 1 and cockatiel 2,respectively, with a color map and identical density scale (right sideof image). Each color corresponds to a density value that can also berepresented with a numerical value. The reddish-brown color indicatesthe greatest density while blue indicates the lowest density. Bothsubjects can be compared directly. The black arrows point to regionsthat are brighter in FIG. 3A compared to 3C. The density scale can alsobe narrowed which makes the density readings more sensitive for thoseareas with decreased density. FIGS. 3B and 3D demonstrate a narroweddensity scale that increases subtleties in the images. Again, bothsubjects are shown at identical density scales. The arrows are placed toallow for direct comparison of color based densities between the twosubjects. The arrows point to greater density readings (as shown withincreased reddish-brown and yellow) in FIG. 3B compared to the sameregions on FIG. 3D (more white and blue representing lower density). Inthis example, bird 1 (represented by FIGS. 3A-3B) has much greater bonedensity than the bird represented by FIGS. 3C-3D. However, thisdifference is not readily observable in plain radiographs. The colorscheme is directly tied to numeric values and can be compared betweensubjects and machines. The color representation allows for quickassessment of density. Even if the scale (and corresponding colors) ischanged, the numeric values are consistently reported (as long as thearea being measured is not over or undersaturated). The numeric valuesallow for reporting that can be compared to “normals” and “abnormals”without the risk of over or under interpreting the color map.

Example 4

A validation study of hardware-software methodology is conducted to testhow well it performs under various conditions of normal usage ondifferent X-ray equipment. To provide a basis for comparison, “phantoms”(objects for test scans) are constructed that correspond to large,medium and small-size animals or human tissues. CT scans are performedon the phantoms to obtain absolute quantification of their radio-opacityvalues. Moreover, 4 duplicate sets of the backing boards, calibrationbars, and phantoms are sent to 10-24 selected veterinary clinics aroundthe country for trial scans on different equipment. The scans obtainedfrom different sites are compared and the results may be used to improvethe robustness of the post-analysis algorithm with a goal is to obtainquantitative X-ray radiograph values that are consistent within 5%across different scanners at different sites. Additional veterinary andhuman hospitals and other testing centers may be recruited to aid inproduct improvement.

Example 5

A study of 4 sets of birds (2 species, each under 2 sets of conditions)using the inventive Radiograph Density Detection Device (RDDD) and amicro computerized tomography (μCT). The μCT will serve as the goldstandard. Data is collected on all birds at two separate times.

The study is designed to accomplish two goals: correlate the RDDD to μCTand collect bone density readings between the different groups of birds.As a tertiary goal, the study serves as a model of how the RDDD can beused on a large scale basis.

Data points collected are used to form a best fit model on theradiographs compared to μCT, to determine how reliable the RDDD data isat specific points on the radiographs and to provide a correlationcoefficient with μCT.

Example 6

Clinical use of the Radiograph Density Detection Device (RDDD) todevelop normal and abnormal density ranges for specific tissues/items,study individuals/single items and populations/groups.

The test may be used as a typical component of X-ray testing whether forscreening, diagnostic or monitoring purposes.

The development of normal and abnormal density ranges may be used as adiagnostic tool and as a long term ongoing means to develop and refinewhat normal density is for the specific subject being studied. Forexample, the RDDD may be used to collect data on bone density values fora population of people living in a certain local. In an alternativeexample, the RDDD could be used to monitor environmental degradation ofselect minerals or metals after exposure to acids and othercontaminants.

Example 7

Studies may be based on data gathered using the RDDD system. The datagenerated by embodiments of the RDDD system could provide a large amountof information relating to individuals (such as people), populations(such as captive animals), construction materials (as with weatheringand mineral leaching of materials) and more. Examples of such studies inhumans and animals include but are not limited to relating bone densityto inactivity; obesity; cage or space confinement; subzero, zero orincreased gravity; nutrition; whole organism or organ specificdevelopment, and much more.

The foregoing description is illustrative of particular embodiments ofthe invention, but is not meant to be a limitation upon the practicethereof. The following claims, including all equivalents thereof, areintended to define the scope of the invention.

The invention claimed is:
 1. A system for radiographic tissue densityevaluation, said system comprising: a cassette configured to be exposedto an X-ray source and configured to obtain information to performintensity standardization of a captured radiographic image of a subject,the cassette having a minimally radio-opaque backing with a spatialhomogeneous X-ray radiographic signature used to estimate asource-detector geometrical inhomogeneity; a calibration bar with apredetermined radiographic signature on or within the cassette to serveas reference for performing the intensity standardization; and asoftware program to analyze and display the captured radiographic image.2. The system of claim 1, wherein the minimally radio-opaque backing ismade of acrylic polymer or other radiolucent material, having a uniformthickness.
 3. The system of claim 1, wherein the calibration bar furthercomprises a graduated radio-opacity inset of standard density items toform a reference range for an entire dynamic range of X-ray exposure. 4.The system of claim 1, wherein the display further comprises acolor-coded intensity image that forms an intuitive colormap based onthe calibration bar.
 5. The system of claim 1, wherein the softwareprogram is installed on a server or a computer that is located in thelocation of the X-ray radiography machine.
 6. The system of claim 1,wherein the software program is installed on a remote server accessedover the Internet.
 7. The system of claim 1, wherein the softwareprogram is offered as a software on-demand service in the cloud that isaccessed over the Internet.